Midline axon guidance in the Drosophila embryonic central nervous system.

Studies in the fruit fly Drosophila melanogaster have provided many fundamental insights into the genetic regulation of neural development, including the identification and characterization of evolutionarily conserved axon guidance pathways and their roles in important guidance decisions. Due to its highly organized and fast-developing embryonic nervous system, relatively small number of neurons, and molecular and genetic tools for identifying, labeling, and manipulating individual neurons or small neuronal subsets, studies of axon guidance in the Drosophila embryonic CNS have allowed researchers to dissect these genetic mechanisms with a high degree of precision. In this review, we discuss the major axon guidance pathways that regulate midline crossing of axons and the formation and guidance of longitudinal axon tracts, two processes that contribute to the development of the precise three-dimensional structure of the insect nerve cord. We focus particularly on recent insights into the roles and regulation of canonical midline axon guidance pathways, and on additional factors and pathways that have recently been shown to contribute to axon guidance decisions at and near the midline.

Effects of Supplemental Diet during Breeding on Fertility, Litter Size, Survival Rate, and Weaning Weight in Mice (Mus musculus).

The addition of supplemental diets to laboratory animals, specifically rodents, is a common practice for the provision of additional nutritional support. We set out to investigate whether the use of commercially available supplemental diets during breeding affected fertility rate, litter size, pup health, and pup survival. Genetically modified female breeding mice with a C57BL/6 background were divided into 3 groups (n = 16 per group) that received standard rodent chow alone or standard rodent chow with one of 2 commercially available supplemental diets: Love Mash (Bio-Serv) extruded pellet or Nutra-Gel (Bio-Serv) diet gel. Male and female mice began receiving the supplemental diet 1 wk before being paired with a partner of the same supplemental group. The mice were allowed to breed for 1 wk before separation from the male. The dams were continued on the diet until all pups were weaned. Overall, breeding dams supplemented with the Love Mash diet experienced significantly greater reproductive success rates and pup survivability compared with the standard diet control group. Dams supplemented with either of the 2 supplemental diets supported significantly larger litters compared with the standard diet control group. Furthermore, Love Mash supplemented diet groups produced significantly larger pups compared with the Nutra-Gel supplemented groups. This study demonstrates that supplemental diets given 1 wk before breeding and continued throughout gestation, parturition, and weaning significantly improved reproductive success, increased litter sizes, and supported pup health and survival.

Computational Design of Phosphotriesterase Improves V-Agent Degradation Efficiency.

Organophosphates (OPs) are a class of neurotoxic acetylcholinesterase inhibitors including widely used pesticides as well as nerve agents such as VX and VR. Current treatment of these toxins relies on reactivating acetylcholinesterase, which remains ineffective. Enzymatic scavengers are of interest for their ability to degrade OPs systemically before they reach their target. Here we describe a library of computationally designed variants of phosphotriesterase (PTE), an enzyme that is known to break down OPs. The mutations G208D, F104A, K77A, A80V, H254G, and I274N broadly improve catalytic efficiency of VX and VR hydrolysis without impacting the structure of the enzyme. The mutation I106 A improves catalysis of VR and L271E abolishes activity, likely due to disruptions of PTE's structure. This study elucidates the importance of these residues and contributes to the design of enzymatic OP scavengers with improved efficiency.